The long-term objectives of this research are: 1) to define the fate of inhaled particles within the human respiratory tract; 2) to characterize the transport of inhaled particles as a function of respiratory flow and airway and airspace sizes; 3) to apply aerosols in diagnostic protocols for the identification of the early effects of inhaled pollutants on lung epithelia and/or to identify individuals who may be especially sensitive to inhaled chemicals. The research proposed here will extend our past and current work on regional deposition in humans into: 1) its application for the in vivo measurement of airway and airspace size changes resulting from single and repetitive daily exposures to inhaled irritants in the rabbit; and 2) studies of comparative aerosol behavior, deposition and responses to inhaled cigarette smoke and other irritants in the lungs of humans and an experimental animal, the rabbit. Specific aims include: 1) To determine the influence of airway branching and flow patterns on distributions of particles using single pathway airway casts of humans and rabbits; 2) To extend and refine aerosol probe techniques for efficient detection and characterization of early changes in airway morphology in humans and laboratory animals; 3) To determine the effects of transient bronchoconstriction induced by cold air, SO2, and cigarette smoke on aerosol dispersion in humans and rabbits; and 4) To determine the influence of early morphological changes in lung airways caused by low-level chronic pollutant exposures on aerosol dispersion and respiratory function in humans and animals, and their exposure-response relationships. The diagnostic tests with aerosols will provide powerful new tools for: 1) examination, in laboratory animals, of the factors involved in the pathogenesis and progression of chronic lung disease; and 2) environmental epidemiology, by relating inhalation exposures to loss of lung functional capacity and/or changes in the distribution of airflow. The comparative studies of aerosol deposition and irritant responses in humans and animals will strengthen the value of the animal model for studying mechanisms of pollutant damage to lung epithelia, and as an efficient test system for characterizing the influence of pollutant, environmental and constitutional factors on responses.